Several experimental problems are encountered in attempts to aroylate N-substituted pyrroles in the .alpha.-position which prevent high yields from being obtained. One such problem relates to the resulting alpha- and beta-isomer distribution of aroylated products. It is well known that electrophilic attack occurs more readily at the alpha- than at the beta-position of heteroaromatic 5-membered rings with one heteroatom. However, among such heterocycles, pyrroles have been reported [see Int. J. Sulfur Chem., C, 7, 64 (1972)] as giving the poorest ratio of .alpha.-isomer to .beta.-isomer in electrophilic substitution reactions (furan&gt; thiophene&gt;&gt;pyrrole).
Another problem relates to the use of acylation catalysts. Coordination of the pyrrole nitrogen with Lewis acids generally used as catalysts in a Friedel-Crafts type of reaction hinders the reaction. Furthermore, use of stronger Lewis acid catalysts, such as aluminum chloride, can induce polymerization of pyrroles. While examples of uncatalyzed acylations of N-substituted pyrroles with aliphatic acylating agents are known [e.g., see Ber. 47, 2427 (1910); Liebigs. Ann. Chem., 721, 105 (1969)], their reaction with aromatic acylating agents in the absence of catalyst has not been reported. Aroylation of N-unsubstituted pyrroles have been carried out using bases [e.g., see Liebigs. Ann. Chem., 724, 137 (1969) and 733, 27 (1970)]. The base acts by extracting a proton from the ring nitrogen and in such reactions, the pyrrole anion is the reactive intermediate. This type of reactivity, however, is not possible when the nitrogen atom bears a substituent.
The aroylation of 1-alkylpyrrole-2-acetic acid derivatives through a Friedel-Crafts type of reaction with AlCl.sub.3 catalysts has been described in U.S. Pat. No. 3,752,826. However, low yields and formation of substantial quantities of the unwanted beta-isomer are typical of this reaction [see J. Med. Chem., 14, No. 7, 647 (1971)].
The non-catalyzed process of this invention constitutes an improvement in making the .alpha.-aroylated pyrroles of formula (I) over the conventional catalyzed methods. Not only are economic savings realized by elimination of the catalyst, but improved yields of product (I) are obtained substantially free of the corresponding .beta.-aroyl isomers.